USP14 is a deubiquitinating enzyme which presents reversible association with proteasome, and can inhibit the proteasome activity via trimming K48 ubiquitin chains on the proteasome‐bound substrates.36, 37 Recent study revealed that USP14 could be phosphorylated and activated by AKT, and could negatively regulate autophagy in neurodegenerative diseases.32, 38 Herein, we validated that SPAG5‐AS1 regulated the de‐ubiquitination of SPAG5 relying on USP14, and therefore activated AKT/mTOR signalling. Here, MTOR is linked to neurodegenerative disease.